Exploring the potentiality of standard sirens to probe cosmic opacity at high redshifts

In this work, using the Gaussian process, we explore the potentiality of future gravitational wave (GW) measurements to probe cosmic opacity at high redshifts through comparing its opacity-free luminosity distance (LD) with the opacity-dependent one from the combination of Type Ia supernovae (SNIa) and gamma-ray bursts (GRBs). The GW data, SNIa and GRB data are simulated from the measurements of the future Einstein Telescope, the actual Pantheon compilation and the latest observation of GRBs compiled by L. Amati {\it et al}, respectively. A nonparametric method is proposed to probe the spatial homogeneity of cosmic transparency at high redshift by comparing the LD reconstructed from the GW data with that reconstructed from the Pantheon and GRB data. In addition, the cosmic opacity is tested by using the parametrization for the optical depth, and the results show that the constraints on cosmic opacity are more stringent than the previous ones. It shows that the future GW measurements may be used as an important tool to probe the cosmic opacity in the high redshift region.Comment: 21pages, 3 figures accepted by EPJC. arXiv admin note: text overlap with arXiv:1912.0232

The Role of Tumour Metabolism in Cisplatin Resistance

Cisplatin is a chemotherapy drug commonly used in cancer treatment. Tumour cells are more sensitive to cisplatin than normal cells. Cisplatin exerts an antitumour effect by interfering with DNA replication and transcription processes. However, the drug-resistance properties of tumour cells often cause loss of cisplatin efficacy and failure of chemotherapy, leading to tumour progression. Owing to the large amounts of energy and compounds required by tumour cells, metabolic reprogramming plays an important part in the occurrence and development of tumours. The interplay between DNA damage repair and metabolism also has an effect on cisplatin resistance; the molecular changes to glucose metabolism, amino acid metabolism, lipid metabolism, and other metabolic pathways affect the cisplatin resistance of tumour cells. Here, we review the mechanism of action of cisplatin, the mechanism of resistance to cisplatin, the role of metabolic remodelling in tumorigenesis and development, and the effects of common metabolic pathways on cisplatin resistance

Impact of old age on resectable colorectal cancer outcomes

Objective This study was performed to identify a reasonable cutoff age for defining older patients with colorectal cancer (CRC) and to examine whether old age was related with increased colorectal cancer-specific death (CSD) and poor colorectal cancer-specific survival (CSS). Methods A total of 76,858 eligible patients from the surveillance, epidemiology, and end results (SEER) database were included in this study. The Cox proportional hazard regression model and the Chow test were used to determine a suitable cutoff age for defining the older group. Furthermore, a propensity score matching analysis was performed to adjust for heterogeneity between groups. A competing risk regression model was used to explore the impact of age on CSD and non-colorectal cancer-specific death (non-CSD). Kaplan–Meier survival curves were plotted to compare CSS between groups. Also, a Cox regression model was used to validate the results. External validation was performed on data from 1998 to 2003 retrieved from the SEER database. Results Based on a cutoff age of 70 years, the examined cohort of patients was classified into a younger group (n = 51,915, <70 years of old) and an older group (n = 24,943, ≥70 years of old). Compared with younger patients, older patients were more likely to have fewer lymph nodes sampled and were less likely to receive chemotherapy and radiotherapy. When adjusted for other covariates, age-dependent differences of 5-year CSD and 5-year non-CSD were significant in the younger and older groups (15.84% and 22.42%, P < 0.001; 5.21% and 14.21%, P < 0.001). Also an age of ≥70 years remained associated with worse CSS comparing with younger group (subdistribution hazard ratio, 1.51 95% confidence interval (CI) [1.45–1.57], P < 0.001). The Cox regression model as a sensitivity analysis had a similar result. External validation also supported an age of 70 years as a suitable cutoff, and this older group was associated with having reduced CSS and increased CSD. Conclusions A total of 70 is a suitable cutoff age to define those considered as having elderly CRC. Elderly CRC was associated with not only increased non-CSD but also with increased CSD. Further research is needed to provide evidence of whether cases of elderly CRC should receive stronger treatment if possible

Identification of an immunogenic DKK1 long peptide for immunotherapy of human multiple myeloma

Dickkopf-1 (DKK1), broadly expressed by tumor cells from human multiple myeloma (MM) and other cancers but absent from most normal tissues, may be an ideal target for immunotherapy. Our previous studies have shown that DKK1 (peptide)-specific cytotoxic T lymphocytes can effectively lyse primary MM cells in vitro. To develop DKK1-based vaccines that can be easily and inexpensively made and used by all patients, we identified a DKK1 long peptide (LP), DKK13-76-LP, that contains 74 amino acids and epitopes that can potentially bind to all major MHC class I and II molecules. Using HLA-A*0201- and HLA-DR*4-transgenic mouse models, we found that DKK1-specific CD4+ and CD8+ T cell responses, detected by DKK1 short peptide (P20 and P66v)-HLA-A*0201 tetramer staining and cytotoxic assay for CD8+ T cells or by CSFE dilution and IFN-a; secretion for CD4+ T cells respectively, can be induced in vivo by immunizing mice with the DKK13-76-LP. In addition, DKK13-76-LP also induced anti-DKK1 humoral immunity in the transgenic mice and the DKK1 antibodies were functional. Finally, DKK13-76-LP stimulated human blood T cells ex vivo to generate DKK1-specific CD4+ and CD8+ T cell responses from eight out of ten MM patients with different MHC backgrounds. The generated DKK1-specific CD8+ cells efficiently lysed autologous MM cells from these patients. Thus, these results confirm the immunogenicity of the DKK13-76-LP in eliciting DKK1-specific CD4+ and CD8+ T cell responses in vitro and in vivo, and suggest that the DKK13-76-LP can be used for immunotherapy of MM and other cancers

Clinicopathological Features and Prognostic Factors of Colorectal Neuroendocrine Neoplasms

Background. Limited research is available regarding colorectal NENs and the prognostic factors remain controversial. Materials and Methods. A total of 68 patients with colorectal NENs were studied retrospectively. Clinical characteristics and prognosis between colonic and rectal NENs were compared. The Cox regression models were used to evaluate the predictive capacity. Results. Of the 68 colorectal NENs patients, 43 (63.2%) had rectal NENs, and 25 (36.8%) had colonic NENs. Compared with rectal NENs, colonic NENs more frequently exhibited larger tumor size (P<0.0001) and distant metastasis (P<0.0001). Colonic NENs had a worse prognosis (P=0.027), with 5-year overall survival rates of 66.7% versus 88.1%. NET, NEC, and MANEC were noted in 61.8%, 23.5%, and 14.7% of patients, respectively. Multivariate analyses revealed that tumor location was not an independent prognostic factor (P=0.081), but tumor size (P=0.037) and pathological classification (P=0.012) were independent prognostic factors. Conclusion. Significant differences exist between colonic and rectal NENs. Multivariate analysis indicated that tumor size and pathological classification were associated with prognosis. Tumor location was not an independent factor. The worse outcome of colonic NENs observed in clinical practice might be due not only to the biological differences, but also to larger tumor size in colonic NENs caused by the delayed diagnosis

Case report: Circulating tumor DNA technology displays temporal and spatial heterogeneity in Waldenström macroglobulinemia during treatment with BTK inhibitors

Background: Waldenström macroglobulinemia (WM) is a rare subtype of B-cell lymphoma. Rituximab-based combination therapy and Bruton’s tyrosine kinase (BTK) inhibitors have greatly improved the prognosis of WM. Despite the high response rate and good tolerance of BTK inhibitors in treatment of WM, a proportion of patients still experience disease progression.Case presentation: We report a 55-year-old man with relapsed WM. The patient achieved partial remission after six courses of CHOP chemotherapy and multiple plasma exchanges in initial treatment. He was admitted to the hospital with abdominal distension, and was diagnosed with relapsed WM and subsequently started on zanubrutinib. Disease progression and histological transformation occurred during treatment. We performed liquid biopsies on transformed plasma, tumor tissue and ascites at the same time and found high consistency between ascites and tissues. Moreover, we detected resistance mutations of BTK inhibitors (BTK, PLCG2) in ascites that were not detected in plasma or tissue. Eventually, the patient died during the 15-month follow-up after relapse.Conclusion: We describe a rare case of WM transformation to DLCBCL treated with chemoimmunotherapy and BTK inhibition. We analyzed tumor DNA obtained at different anatomic sites and circulating tumor DNA (ctDNA) derived from plasma and ascites specimens, with apparent significant temporal and spatial heterogeneity. The case specifically highlights the clinical value of ctDNA of ascites supernatant from WM patients, which is a more convenient and relatively noninvasive method compared with traditional invasive tissue biopsy

MOPAT: a graph-based method to predict recurrent cis-regulatory modules from known motifs

The identification of cis-regulatory modules (CRMs) can greatly advance our understanding of eukaryotic regulatory mechanism. Current methods to predict CRMs from known motifs either depend on multiple alignments or can only deal with a small number of known motifs provided by users. These methods are problematic when binding sites are not well aligned in multiple alignments or when the number of input known motifs is large. We thus developed a new CRM identification method MOPAT (motif pair tree), which identifies CRMs through the identification of motif modules, groups of motifs co-ccurring in multiple CRMs. It can identify ‘orthologous’ CRMs without multiple alignments. It can also find CRMs given a large number of known motifs. We have applied this method to mouse developmental genes, and have evaluated the predicted CRMs and motif modules by microarray expression data and known interacting motif pairs. We show that the expression profiles of the genes containing CRMs of the same motif module correlate significantly better than those of a random set of genes do. We also show that the known interacting motif pairs are significantly included in our predictions. Compared with several current methods, our method shows better performance in identifying meaningful CRMs